Population Pharmacokinetics/Pharmacodynamics (PK/PD) of Microemulsion Propofol in Healthy Volunteers

AquafolTM (Daewon Pharmaceutical Co., Ltd., Seoul, Korea) is a microemulsion propofol that has been developed for eliminating lipid solvent-related adverse events of long chain triglyceride emulsion (LCT) propofol (Diprivan®; AstraZeneca, London, United Kingdom), such as infection, fat embolism, hypertriglyceridemia and pancreatitis. Originally, AquafolTM was formulated with 8% polyethylene glycol 660 hydroxystearate (Solutol HS 15, BASF Company Ltd., Seoul, Korea) and 5% tetrahydrofurfuryl alcohol polyethylene glycol ether (Glycofurol, Roche, Basle, Switzerland). A phase 1 study to assess the safety and tolerability of polymeric vehicles of this formulation in healthy volunteers showed dose-limiting toxicity. Subsequently, it was reformulated with 10% purified poloxamer 188 (PP188) as a nonionic block copolymer surfactant and 0.7% polyethylene glycol 660 hydroxystearate as a nonionic surfactant. Alterations in propofol formulation may result in altered pharmacokinetic, pharmacodynamic characteristics.

The aim of this study was to compare the pharmacokinetics and pharmacodynamics of propofol microemulsion and lipid emulsion, using noncompartmental analysis and population analysis with mixed effects modeling.

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Key information

Conditions

Healthy

Age range

19 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Asan Medical Center

Seoul, 138-736, South Korea

About this study

The Subjects fasted for 6 h before study drug administration. An 18-gauge angiocatheter was placed in a vein of the antecubital area. A second angiocatheter was placed in the contralateral radial artery for frequent blood sampling. Subjects were monitored with electrocardiography, pulse oximetry, end-tidal carbon dioxide concentration, and invasive blood pressure measurement (Datex-Ohmeda S/5;Planar Systems, Inc., Beaverton, OR) and Bispectral Index (BIS) (Aspect 2000; Aspect Medical Systems, Inc., Newton,MA). In addition, the electroencephalographic activity of seven monopolar channels (Fp1, Fp2, F3, F4, Cz, P3, and P4, referenced by A2) was recorded by QEEG-8 (LXE3208, Laxtha Inc., Daejeon, Korea).

The subjects were stratified into three age groups (19-40, 41-64, and > 65 yr), and each group included 10 male and 10 female volunteers. Each subject received both propofol formulations in a crossover fashion separated by a 7-day washout period, and the order of the drug administration was randomized. Subjects received both propofol formulations during 60 min. The infusion rate was assigned according to a nonblinded, randomized design to 1.5, 3, 6, or 12 mg/kg/hr.

Samples were collected in ethylenediaminetetraacetic acid (EDTA) tube and centrifuged for 10 min at 3,500rpm. Plasma was stored at -70°C until assay. Arterial blood samples (4 ml) were taken at preset intervals: 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 10, 15, 20, 30, 40, 50, 58, 60, 62, 66, 70, 80, 90, 120 and 150 min after administration of propofol. Venous blood samples (4ml) were taken at preset intervals: 180, 240, 300, 600, 720 and 1,200 min after administration of propofol. In addition, arterial samples were drawn when LOC (loss of consciousness) and ROC (recovery of consciousness) were observed.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

ASA 1 or 2 (healthy or mild systemic illness) healthy volunteers
age ≥ 19 yr

Exclusion criteria

ASA 3 or above
out with age group above
contraindications against the use of propofol
abnormal laboratory finding with clinical significance
evidence of pregnancy
history of alcohol or drug abuse
neurological or psychiatric disease
unable or unwilling to give informed consent

Treatment and study plan

Propofol

Drug

Each subject received both propofol formulations in a crossover fashion separated by a 7-day washout period, and the order of the drug administration was randomized. Subjects received both propofol formulations (Lipid emulsion propofol: Diprivan® and Microemulsion propofol: AquafolTM) during 60 min. The infusion rate was assigned according to a nonblinded, randomized design to 1.5, 3, 6, or 12 mg/kg/hr.

Other names: Microemulsion propofol: AquafolTM, Lipid emulsion propofol: Diprivan®

Primary outcomes

The aim of this study was to compare the pharmacokinetics and pharmacodynamics of microemulsion and lipid emulsion propofol.

Time frame: Between 5/2/2009 until 5/31/2010

Sponsors and collaborators

Lead sponsor

Asan Medical Center

Other

Registry information

Official study title

Population Pharmacokinetic and Pharmacodynamic Modeling of Microemulsion Propofol in Healthy Volunteers: Comparison With Lipid Emulsion Propofol

Important dates

Study start: 2009
Primary completion: 2010
Study completion: 2011
First posted: May 27, 2009
Registry last updated: Jan 20, 2012

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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Completed